Serglycin as a potential diagnostic biomarker for hemangiosarcoma in dogs

Hemangiosarcoma (HSA) is a common splenic malignant neoplasia in dogs, originating from the endothelium. The tumor has an aggressive character, and the clinical symptoms of HSA are mostly due to the secondary effects of the tumor such as tumor growth or rupture. The prognosis is poor for HSA, usu...

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Autor principal: Linder, Cassandra
Formato: H3
Lenguaje:Inglés
sueco
Publicado: SLU/Dept. of Clinical Sciences (until 231231) 2022
Materias:
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author Linder, Cassandra
author_browse Linder, Cassandra
author_facet Linder, Cassandra
author_sort Linder, Cassandra
collection Epsilon Archive for Student Projects
description Hemangiosarcoma (HSA) is a common splenic malignant neoplasia in dogs, originating from the endothelium. The tumor has an aggressive character, and the clinical symptoms of HSA are mostly due to the secondary effects of the tumor such as tumor growth or rupture. The prognosis is poor for HSA, usually with a survival time of under one year. It is challenging to distinguish HSA from benign neoplasias in the spleen, such as hematoma, which has a significantly better prognosis. Hence, many dogs are euthanized today due to suspicion of splenic HSA. With better diagnostic methods, several of these dogs could be cured as the tentative diagnosis may not be correct. Biomarkers have been discussed as a diagnostic method for HSA. As of today, few biomarkers have been evaluated and somewhat successfully implemented as a diagnostic method in the clinic. Serglycin is a proteoglycan that is mainly expressed by immune cells and have shown, in humans, a correlation between increased expression and malignant cancers. Hence, a quantification of serglycin in tumor canine patients could thus indicate tumor malignancy and be used for diagnostic purposes. In this study, serglycin expression was analyzed in splenic HSA tissue and non-pathological splenic tissue from formalin-fixed and paraffin-embedded material from dogs. Another gene, Eukaryotic elongation factor 2 (EEF2), was also included in the study to be compared with the expression of serglycin. The analysis was performed in real time with quantitative polymerase chain reaction (qPCR), where the expression in the tumor samples were compared with the healthy samples. Even though the quality of the qPCR results from the samples varied, this thesis still shows that there are trends that are interesting to continue to investigate with other methods and a larger patient material as a basis. Based on the samples showing the correct expression, this study support that splenic HSA tissue expresses significantly higher levels of serglycin than the non-pathological splenic tissue. This was not the case for EEF2, suggesting that serglycin is a more suitable biomarker for HSA than EEF2. However, before serglycin can be used as a biomarker at the clinic, more samples need to be analyzed to map out the normal variation in dogs. Also, as HSA was now compared with healthy spleens, it would be valuable to compare splenic HSA with other benign splenic masses as well. Lastly, a simple and inexpensive way of measuring the serglycin expression needs to be developed.
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spelling RepoSLU177492023-01-21T00:22:17Z Serglycin as a potential diagnostic biomarker for hemangiosarcoma in dogs Serglycin som en potentiell diagnostisk biomarkör för hemangiosarkom hos hundar Linder, Cassandra Serglycin EEF2 cancer hemangiosarcoma dog canine metastatic biomarker qPCR Hemangiosarcoma (HSA) is a common splenic malignant neoplasia in dogs, originating from the endothelium. The tumor has an aggressive character, and the clinical symptoms of HSA are mostly due to the secondary effects of the tumor such as tumor growth or rupture. The prognosis is poor for HSA, usually with a survival time of under one year. It is challenging to distinguish HSA from benign neoplasias in the spleen, such as hematoma, which has a significantly better prognosis. Hence, many dogs are euthanized today due to suspicion of splenic HSA. With better diagnostic methods, several of these dogs could be cured as the tentative diagnosis may not be correct. Biomarkers have been discussed as a diagnostic method for HSA. As of today, few biomarkers have been evaluated and somewhat successfully implemented as a diagnostic method in the clinic. Serglycin is a proteoglycan that is mainly expressed by immune cells and have shown, in humans, a correlation between increased expression and malignant cancers. Hence, a quantification of serglycin in tumor canine patients could thus indicate tumor malignancy and be used for diagnostic purposes. In this study, serglycin expression was analyzed in splenic HSA tissue and non-pathological splenic tissue from formalin-fixed and paraffin-embedded material from dogs. Another gene, Eukaryotic elongation factor 2 (EEF2), was also included in the study to be compared with the expression of serglycin. The analysis was performed in real time with quantitative polymerase chain reaction (qPCR), where the expression in the tumor samples were compared with the healthy samples. Even though the quality of the qPCR results from the samples varied, this thesis still shows that there are trends that are interesting to continue to investigate with other methods and a larger patient material as a basis. Based on the samples showing the correct expression, this study support that splenic HSA tissue expresses significantly higher levels of serglycin than the non-pathological splenic tissue. This was not the case for EEF2, suggesting that serglycin is a more suitable biomarker for HSA than EEF2. However, before serglycin can be used as a biomarker at the clinic, more samples need to be analyzed to map out the normal variation in dogs. Also, as HSA was now compared with healthy spleens, it would be valuable to compare splenic HSA with other benign splenic masses as well. Lastly, a simple and inexpensive way of measuring the serglycin expression needs to be developed. Hemangiosarkom (HS) är en vanlig malign neoplasi i mjälten hos hundar som härrör från endotelet. Tumören har en aggressiv karaktär och de kliniska symtomen på HS beror främst på tumörens sekundära effekter såsom tumörtillväxt eller bristning. Prognosen är dålig för HS, vanligtvis med en överlevnadstid på under ett år. När det gäller massor i mjälten är det utmanande att skilja HS från benigna neoplastiska förändringar, såsom hematom, som har en betydligt bättre prognos. Vid misstanke om HS i mjälten avlivas många hundar idag, då prognosen är dålig samt operationen kostsam. Med bättre diagnostiska metoder skulle flera av dessa hundar kunna botas eftersom den preliminära diagnosen kanske inte är korrekt. Biomarkörer har diskuterats som en diagnostisk metod för HS. Dock har få biomarkörer utvärderats, samt framgångsrikt implementerats, som diagnostisk metod på kliniknivå idag. Serglycin är en proteoglykan som huvudsakligen uttrycks av immunceller och som hos människor har visat ett samband mellan ökat uttryck och maligna cancerformer. En kvantifiering av serglycin hos tumörpatienter hos hundar skulle således kunna indikera maligna tumörer och användas för diagnostiska ändamål. I denna studie analyserades serglycin uttrycket i vävnadsprover från mjältar med HS samt från frisk mjältvävnad från formalinfixerat och paraffininbäddat material från hundar. En annan gen, ”Eukaryotic elongation factor 2” (EEF2), inkluderades även i studien för att jämföras med uttrycket av serglycin. Analysen utfördes i realtid med " quantitative polymerase chain reaction” (qPCR) där uttrycket i tumörproverna jämfördes med den friska mjältvävnaden. Resultaten från denna studie visar att mjältvävnad med HS uttrycker högre nivåer av serglycin jämfört med frisk mjältvävnad, vilket är i linje med resultat från tidigare studier på människor. EEF2 visade inte ett signifikant högre uttryck i mjältvävnaden med HS jämfört med den friska mjältvävnaden. Detta indikerar att serglycin är en mer lämplig biomarkör för HS än EEF2. Dock behöver fler prover analyseras och jämföras med normal vävnad för att få mer kunskap om normalvariationen i serglycin uttrycket hos hundar. Eftersom HSA nu jämfördes med friska mjältar, skulle det också vara värdefullt att jämföra serglycin uttrycket från HS med andra benigna mjältmassor. Slutligen måste även ett enkelt och billigt sätt att mäta uttrycket utvecklas. SLU/Dept. of Clinical Sciences (until 231231) 2022 H3 eng swe https://stud.epsilon.slu.se/17749/
spellingShingle Serglycin
EEF2
cancer
hemangiosarcoma
dog
canine
metastatic
biomarker
qPCR
Linder, Cassandra
Serglycin as a potential diagnostic biomarker for hemangiosarcoma in dogs
title Serglycin as a potential diagnostic biomarker for hemangiosarcoma in dogs
title_full Serglycin as a potential diagnostic biomarker for hemangiosarcoma in dogs
title_fullStr Serglycin as a potential diagnostic biomarker for hemangiosarcoma in dogs
title_full_unstemmed Serglycin as a potential diagnostic biomarker for hemangiosarcoma in dogs
title_short Serglycin as a potential diagnostic biomarker for hemangiosarcoma in dogs
title_sort serglycin as a potential diagnostic biomarker for hemangiosarcoma in dogs
topic Serglycin
EEF2
cancer
hemangiosarcoma
dog
canine
metastatic
biomarker
qPCR